Heterocyclic-substituted phenyl methanones

Abstract

The present invention relates to compounds of formula I wherein R 1 , R 2 , and are defined in the specification and to pharmaceutically acceptable acid addition salts thereof.

1. A compound of formula IA 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is halogen, —OR 1′ , —SR 1″ , cycloalkyl, cyclic amide, heterocycloalkyl, aryl or 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen; 
         R 1′  and R 1″  are each hydrogen, lower alkyl, lower alkyl substituted by halogen, —(CH 2 ) x -cycloalkyl or —(CH 2 ) x -aryl; 
         R 2  is —S(O) 2 -lower alkyl, —S(O) 2 NH-lower alkyl, NO 2  or CN; 
         R 3  is hydrogen, hydroxy, halogen, ═O, lower alkyl, cycloalkyl,
 heterocycloalkyl, lower alkoxy, CN, NO 2 , NH 2 , aryl, 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen, —NH-lower alkyl, —N(lower alkyl) 2 , cyclic amide, —C(O)-cyclic amide, S-lower alkyl, —S(O) 2 -lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, lower alkyl substituted by hydroxy, —O—(CH 2 ) y -lower alkoxy, —O(CH 2 ) y C(O)N(lower alkyl) 2 , —C(O)-lower alkyl, —O—(CH 2 ) x -aryl, —O—(CH 2 ) x -cycloalkyl, —O—(CH 2 ) x -heterocycloalkyl, —C(O)O-lower alkyl, —O(O)—NH-lower alkyl, —C(O)—N(lower alkyl) 2 , 2-oxy-5-aza-bicyclo[2.2.1]hept-5-yl or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; 
 
         R and R′ are each independently hydrogen or lower alkyl; 
         and wherein all aryl-, cycloalkyl-, cyclic amide, heterocycloalkyl- or 5 or 6 membered heteroaryl groups as defined for R 1 , R 1′ , R 1″  and R 3  are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, ═O, halogen, lower alkyl, phenyl, lower alkyl substituted by halogen and lower alkoxy; 
         n is 1 or 2; 
         x is 0, 1 or 2; and 
         y is 1 or 2; 
         or a pharmaceutically acceptable acid addition salt thereof. 
       
     
     
       2. A compound of  claim 1 , wherein R 1  is OR 1′ . 
     
     
       3. A compound of  claim 2 , selected from the group consisting of
 (5,6-dichloro-1,3-dihydro-isoindol-2-yl)-(2-isopropoxy-5-methanesulfonyl-phenyl)-methanone, 
 rac-(5,6-dichloro-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-methanone, 
 (5,6-dichloro-1,3-dihydro-isoindol-2-yl)-(2-isopropylsulfanyl-5-methanesulfonyl-phenyl)-methanone, 
 [5-methanesulfonyl-2-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-methanone, 
 (5-chloro-6-methyl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 (5-chloro-6-methoxy-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 (5-ethylsulfanyl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 (2-isobutoxy-5-methanesulfonyl-phenyl)-(5-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-methanone, and 
 4-isopropoxy-N-methyl-3-(5-trifluoromethyl-1,3-dihydro-isoindole-2-carbonyl)-benzenesulfonamide. 
 
     
     
       4. A compound of  claim 2 , selected from the group consisting of
 (5-chloro-6-methyl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 (5-chloro-6-methyl-1,3-dihydro-isoindol-2-yl)-(2-isobutoxy-5-methanesulfonyl-phenyl)-methanone, 
 (5-chloro-6-ethylsulfanyl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 (2-isopropoxy-5-methanesulfonyl-phenyl)-(5-methoxy-1,3-dihydro-isoindol-2-yl)-methanone, 
 [[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-methyl-6-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-methoxy-6-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-trifluoromethoxy-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(4-methyl-thiazol-2-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(2-methyl-pyridin-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone, and 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(5-methyl-thiophen-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone. 
 
     
     
       5. A compound of  claim 2 , selected from the group consisting of
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-thiazol-2-yl-1,3-dihydro-isoindol-2-yl)-methanone, 
 (5-ethylsulfanyl-6-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 (5-chloro-6-methoxy-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone 
 (5-chloro-6-methoxy-1,3-dihydro-isoindol-2-yl)-(2-isobutoxy-5-methanesulfonyl-phenyl)-methanone, 
 (5-fluoro-6-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 (5-ethoxy-6-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-(2-isopropoxy-5-methanesulfonyl-phenyl)-methanone, 
 (5-chloro-6-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-(2-isobutoxy-5-methanesulfonyl-phenyl)-methanone, 
 (5-chloro-6-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-(2-cyclobutylmethoxy-5-methanesulfonyl-phenyl)-methanone, 
 (2-isopropoxy-5-methanesulfonyl-phenyl)-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone, and 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone. 
 
     
     
       6. A compound of  claim 2 , selected from the group consisting of
 (2-isobutoxy-5-methanesulfonyl-phenyl)-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 (2-cyclopropylmethoxy-5-methanesulfonyl-phenyl)-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 (2-cyclobutylmethoxy-5-methanesulfonyl-phenyl)-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [2-(2,2-dimethyl-propoxy)-5-methanesulfonyl-phenyl]-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-(3,3-difluoro-piperidin-1-yl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(2,2,2-trifluoro-ethyl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[(1R,5S)-5-(3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-methyl-6-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(tetrahydro-furan-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone, and 
 [5-chloro-6-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone. 
 
     
     
       7. A compound of  claim 2 , selected from the group consisting of
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(tetrahydro-pyran-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-pyridin-4-yl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-pyridin-3-yl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-phenyl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-(2-chloro-phenyl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-thiophen-3-yl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(4-methyl-thiophen-2-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(3-methyl-thiophen-2-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-(4-fluoro-phenyl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, and 
 [5-(3-fluoro-phenyl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone. 
 
     
     
       8. A compound of  claim 2 , selected from the group consisting of
 [5-(2-fluoro-phenyl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-(3,5-difluoro-phenyl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-methanesulfonyl-2-(2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(3-methoxy-phenyl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-thiophen-2-yl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(4-methyl-thiophen-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-pyrazol-1-yl-1,3-dihydro-isoindol-2-yl)-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(2,2,2-trifluoro-ethoxy)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-chloro-6-(tetrahydro-furan-3-yl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 rac-(2-isopropoxy-5-methanesulfonyl-phenyl)-[5-(tetrahydro-furan-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone, and 
 rac-[5-methanesulfonyl-2-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-[5-(tetrahydro-furan-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone. 
 
     
     
       9. A compound of  claim 2 , selected from the group consisting of
 rac-(2-isopropoxy-5-methanesulfonyl-phenyl)-[5-(tetrahydro-pyran-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-chloro-6-(3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-methanone, 
 rac-[5-methanesulfonyl-2-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-[5-(tetrahydro-pyran-3-yl)-1,3-dihydro-isoindol-2-yl]-methanone, 
 ((1S,4S)-5-chloro-6-2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-fluoro-6-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-(3-fluoro-oxetan-3-yl)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-[5-(3,3,3-trifluoro-propoxy)-1,3-dihydro-isoindol-2-yl]-methanone, 
 (5-fluoro-6-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, and 
 (5-fluoro-6-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-[5-methanesulfonyl-2-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-methanone. 
 
     
     
       10. A compound of  claim 2 , selected from the group consisting of
 (2-isopropoxy-5-methanesulfonyl-phenyl)-[5-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-methanesulfonyl-2-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-[5-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-methanone, 
 [5-chloro-6-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-chloro-6-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-(2-isopropoxy-5-methanesulfonyl-phenyl)-methanone, 
 [5-fluoro-6-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone, 
 [5-fluoro-6-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-(2-isopropoxy-5-methanesulfonyl-phenyl)-methanone, 
 [5-fluoro-6-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-methanone and 
 [5-chloro-6-(tetrahydro-pyran-4-yloxy)-1,3-dihydro-isoindol-2-yl]-[5-methanesulfonyl-2-(2,2,3,3,3-pentafluoro-propoxy)-phenyl]-methanone. 
 
     
     
       11. A compound of  claim 1 , wherein R 1  is unsubstituted or substituted phenyl. 
     
     
       12. A compound of  claim 11 , selected from the group consisting of
 (5-chloro-6-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-(4-methanesulfonyl-biphenyl-2-yl)-methanone, 
 (5-chloro-6-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-(3′-fluoro-4-methanesulfonyl-biphenyl-2-yl)-methanone, 
 (5-chloro-6-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-(4′-fluoro-4-methanesulfonyl-biphenyl-2-yl)-methanone and 
 (4′-fluoro-4-methanesulfonyl-biphenyl-2-yl)-[5-(tetrahydro-pyran-4-yl)-1,3-dihydro-isoindol-2-yl]-methanone. 
 
     
     
       13. A compound of formula IE 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is halogen, —OR 1′ , —SR 1″ , cycloalkyl, cyclic amide, heterocycloalkyl, aryl or 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen; 
         R 1′  and R 1″  are each independently hydrogen, lower alkyl, lower alkyl substituted by halogen, —(CH 2 ) x -cycloalkyl or —(CH 2 ) x -aryl; 
         R 2  is —S(O) 2 -lower alkyl, —S(O) 2 NH-lower alkyl, NO 2  or CN; 
         R 7  is hydrogen, hydroxy, halogen, ═O, lower alkyl, cycloalkyl,
 heterocycloalkyl, lower alkoxy, CN, NO 2 , NH 2 , aryl, 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen, —NH-lower alkyl, —N(lower alkyl) 2 , cyclic amide, —C(O)-cyclic amide, S-lower alkyl, —S(O) 2 -lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, lower alkyl substituted by hydroxy, —O—(CH 2 ) y -lower alkoxy, —O(CH 2 ) y C(O)N(lower alkyl) 2 , —C(O)-lower alkyl, —O—(CH 2 ) x -aryl, —O—(CH 2 ) x -cycloalkyl, —O—(CH 2 ) x -heterocycloalkyl, —C(O)O-lower alkyl, —C(O)—NH-lower alkyl, —C(O)—N(lower alkyl) 2 , 2-oxy-5-aza-bicyclo[2.2.1]hept-5-yl or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; 
 
         R, R′, R″ and R′″ are independently from each other hydrogen or lower alkyl; or 
         R′ and R″ in group e) together with —(CH 2 ) 4 — form a six membered ring; 
         and wherein all aryl-, cycloalkyl-, cyclic amide, heterocycloalkyl- or 5 or 6 membered heteroaryl groups as defined for R 1 , R 1′ , R 1″  and R 7  are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, ═O, halogen, lower alkyl, phenyl, lower alkyl substituted by halogen and lower alkoxy; 
         q is 1 or 2; 
         x is 0, 1 or 2; and 
         y is 1 or 2; 
         or a pharmaceutically acceptable acid addition salt thereof. 
       
     
     
       14. A compound of  claim 13 , selected from the group consisting of
 1-(4-methanesulfonyl-biphenyl-2-carbonyl)-2,3-dihydro-1H-indole-4-carbonitrile, 
 1-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-benzoyl]-2,3-dihydro-1H-indole-4-carboxylic acid methyl ester, 
 1-(2-isopropoxy-5-methanesulfonyl-benzoyl)-2,3-dihydro-1H!-indole-4-carboxylic acid methyl ester and 
 (4-bromo-2,3-dihydro-indol-1-yl)-[5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-methanone. 
 
     
     
       15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula IA 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is halogen, —OR 1′ , —SR 1″ , cycloalkyl, cyclic amide, heterocycloalkyl, aryl or 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen; 
         R 1′  and R 1″  are each hydrogen, lower alkyl, lower alkyl substituted by halogen, —(CH 2 ) x -cycloalkyl or —(CH 2 ) x -aryl; 
         R 2  is —S(O) 2 -lower alkyl, —S(O) 2 NH-lower alkyl, NO 2  or CN; 
         R 3  is hydrogen, hydroxy, halogen, ═O, lower alkyl, cycloalkyl,
 heterocycloalkyl, lower alkoxy, CN, NO 2 , NH 2 , aryl, 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen, —NH-lower alkyl, —N(lower alkyl) 2 , cyclic amide, —C(O)-cyclic amide, S-lower alkyl, —S(O) 2 -lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, lower alkyl substituted by hydroxy, —O—(CH 2 ) y -lower alkoxy, —O(CH 2 ) y C(O)N(lower alkyl) 2 , —C(O)-lower alkyl, —O—(CH 2 ) x -aryl, —O—(CH 2 ) x -cycloalkyl, —O—(CH 2 ) x -heterocycloalkyl, —C(O)O-lower alkyl, —C(O)—NH-lower alkyl, —C(O)—N(lower alkyl) 2 , 2-oxy-5-aza-bicyclo[2.2.1]hept-5-yl or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; 
 
         R and R′ are each independently hydrogen or lower alkyl; 
         and wherein all aryl-, cycloalkyl-, cyclic amide, heterocycloalkyl- or 5 or 6 membered heteroaryl groups as defined for R 1 , R 1′ , R 1″  and R 3  are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, ═O, halogen, lower alkyl, phenyl, lower alkyl substituted by halogen and lower alkoxy; 
         n is 1 or 2; 
         x is 0, 1 or 2; and 
         y is 1 or 2; 
         or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier. 
       
     
     
       16. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula IE 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is halogen, —OR 1′ , —SR 1″ , cycloalkyl, cyclic amide, heterocycloalkyl, aryl or 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen; 
         R 1′  and R 1″  are each independently hydrogen, lower alkyl, lower alkyl substituted by halogen, —(CH 2 ) x -cycloalkyl or —(CH 2 ) x -aryl; 
         R 2  is —S(O) 2 -lower alkyl, —S(O) 2 NH-lower alkyl, NO 2  or CN; 
         R 7  is hydrogen, hydroxy, halogen, ═O, lower alkyl, cycloalkyl,
 heterocycloalkyl, lower alkoxy, CN, NO 2 , NH 2 , aryl, 5- or 6-membered heteroaryl containing one, two or three heteroatoms selected from the group consisting of oxygen, sulphur and nitrogen, —NH-lower alkyl, —N(lower alkyl) 2 , cyclic amide, —C(O)-cyclic amide, S-lower alkyl, —S(O) 2 -lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, lower alkyl substituted by hydroxy, —O—(CH 2 ) y -lower alkoxy, —O(CH 2 ) y C(O)N(lower alkyl) 2 , —C(O)-lower alkyl, —O—(CH 2 ) x -aryl, —O—(CH 2 ) x -cycloalkyl, —O—(CH 2 ) x -heterocycloalkyl, —C(O)O-lower alkyl, —C(O)—NH-lower alkyl, —C(O)—N(lower alkyl) 2 , 2-oxy-5-aza-bicyclo[2.2.1]hept-5-yl or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; 
 
         R, R′, R″ and R′″ are independently from each other hydrogen or lower alkyl; or 
         R′ and R′″ in group e) together with —(CH 2 ) 4 — form a six membered ring; 
         and wherein all aryl-, cycloalkyl-, cyclic amide, heterocycloalkyl- or 5 or 6 membered heteroaryl groups as defined for R 1 , R 1′ , R 1″  and R 7  are unsubstituted or substituted by one or more substituents selected from the group consisting of hydroxy, ═O, halogen, lower alkyl, phenyl, lower alkyl substituted by halogen and lower alkoxy; 
         q is 1 or 2; 
         x is 0, 1 or 2; and 
         y is 1 or 2; 
         or a pharmaceutically acceptable acid addition salt thereof and a pharmaceutically acceptable carrier.